The present invention relates generally to compositions and methods for the treatment of disease states. More specifically, the present invention relates to compositions and methods for treating or preventing insulin-resistance syndrome (Syndrome X).
Syndrome X is a term that has been given to a group of metabolic abnormalities consisting of multiple metabolic aberrations. These metabolic abnormalities have also been referred to as insulin-resistance syndrome and metabolic syndrome. The metabolic aberrations that fall under the designation Syndrome X include insulin-resistance (impaired glucose tolerance) and hyperinsulinemia. Other concomitant aberrations occurring in Syndrome X may include, but are not limited to, high plasma triglyceride levels, a low high density lipoprotein profile, microvascular angina, hypertension and obesity.
During the past two decades, low-fat high-carbohydrate diets have been advocated by health care professionals. Despite the focus on improved nutrition during this period, society has experienced an increase in the number of individuals becoming obese. One possible explanation for this phenomena may relate to the impaired ability of individuals with the propensity towards Syndrome X to process elevated carbohydrate intake associated with these diets. Thus, these “healthy diets” may actually cause individuals with this syndrome to gain weight. This may be due in part to the insulin resistance associated with Syndrome X.
It has been proposed that one of the underlying factors of Syndrome X includes an inability of the enzyme lipoprotein lipase to effectively clear chylomicrons from the plasma after digestion of dietary fat. It is interesting to note that there is a genetic disorder known as Familial Lipoprotein Lipase Deficiency, which is an autosomal recessive disorder. While homozygous expression of this disorder is uncommon with an occurrence of 1 in a million, the occurrence of the heterozygous form of this disorder is approximately 1 in 500.
Further, heterozygote first-degree relatives of patients with LPL deficiency exhibit a 50% decrease of LPL activity in plasma compared to controls under test conditions, while only exhibiting mild plasma lipid elevations. Additionally, several studies have suggested that association of this disorder or a predilection thereto may be involved in a much wider incidence of associated metabolic disturbances. There may actually be a substantial range of genetically-based lipoprotein lipase response, which may relate to a spectrum of response in individuals susceptible to Syndrome X. Additionally, the interaction of other lifestyle circumstances and metabolic conditions may accentuate this susceptibility.
In patients with Syndrome X, as well as in many patients diagnosed with hypertension, obesity, and type II diabetes, elevated levels of IL-1, IL-6, and TNF-alpha have been reported. IL-6 has been demonstrated to be the main cytokine mediator of the acute-phase response. This action of IL-6 as a prime inducer of acute-phase response, resulting in the action of cytokines on many tissues, may be a major contributor to physiological and clinical features of Syndrome X.
Along with the elevation of these cytokines, patients with Syndrome X may also exhibit elevated glucagon and cortisol concentrations. In patients diagnosed with Syndrome X, there are accompanying metabolic abnormalities, which likely accentuate the expression of Syndrome X by further inhibiting the ability of the body to process glucose optimally. There is evidence of significant variation of tissue sensitivity and response to cortisol in patients with Syndrome X, suggesting that even minimally elevated cortisol levels may be related to hypertension, insulin resistance, glucose intolerance, and hypertriglyceridemia.
The inventors do not believe that there is an effective treatment for patients suffering from Syndrome X.
Accordingly, there is a need for improved methods of treatment and compositions for treating Syndrome X.